Effects of Probiotic Supplement in Pregnant Women with Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Previous studies showed that probiotics could improve glycemic control and attenuate some of the adverse effects of type 2 diabetes. However, whether the effects are generalizable to gestational diabetes mellitus (GDM) remains uncertain. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the effects of probiotic supplement in GDM. METHOD: PubMed, EMBASE, the Cochrane Library, and EBSCO were systematically searched for relevant literature published through January 2019. Randomized controlled trials (RCTs) assessing the effects of probiotic supplement on one or more of the following in GDM were included: pregnancy outcome (the primary outcome), glycemic control, blood lipid profile, and inflammation and oxidative stress. Two reviewers independently extracted data and assessed the risk of bias in studies. Meta-analysis was conducted by using the fixed effects model unless substantial heterogeneity was found among studies. RESULTS: Eleven randomized trials involving 719 participants were included for analysis. Eight of the trials were from Iran. Probiotics were given alone in eight trials and synbiotics in three trials. Though the components of probiotics varied, Lactobacillus was included in all trials and Bifidobacterium in all except one. The duration of intervention ranged from 4 to 8 weeks. Almost all trials (10/11) had a low risk of bias. Probiotic supplementation reduced the risk of a newborn's hyperbilirubinemia by 74% and improved four biomarkers for glycemic control (fasting blood glucose, fasting serum insulin, homeostasis model assessment insulin resistance, and quantitative insulin sensitivity check index), two biomarkers for lipid profile (triglycerides and HDL-cholesterol), and four biomarkers for inflammation and oxidative stress (total glutathione, malondialdehyde, nitric oxide, and total antioxidant capacity). But significant heterogeneity was observed in the meta-analyses on the four biomarkers related to glycemic control and on triglycerides, which could not be explained by prespecified subgroup analyses according to the mean age of participants and intervention type (i.e., probiotics or synbiotics). The effects on the risk of preterm delivery, macrosomia and a newborns' hypoglycemia, gestational age, total cholesterol, and LDL-cholesterol were not statistically significant. CONCLUSION: Probiotic supplementation seemed to be able to reduce the risk of a newborn's hyperbilirubinemia and improve glycemic control, blood lipid profiles and inflammation and oxidative stress in pregnant women with GDM. However, due to the heterogeneity among existing studies, the surrogate nature of outcomes, and/or the fact that most studies were from Iran, the clinical significance and generalizability of the above findings remain uncertain. Further studies are warranted to address the limitations of existing evidence and better inform the management of GDM.